Details of a Researcher - Okamura, Tomonori

Papers - Okamura, Tomonori

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EFFECT OF ACCUMULATED UNHEALTHY BEHAVIORS ON INSOMNIA(A)over-cap(SIC).LIFESTYLE-RELATED DISEASE DIFFERENCES IN A JAPANESE COMMUNITY POPULATION

Kato Suzuka, Harada Sei, Iida Miho, Kuwabara Kazuyo, Sugiyama Daisuke, Takeuchi Ayano, Hirata Aya, Sata Mizuki, Matsumoto Minako, Kurihara Ayako, Okamura Tomonori, Takebayashi Toru

SLEEP 44 A128 - A128 2021.05

Research paper (scientific journal), ISSN 0161-8105

Reliability of urinary charged metabolite concentrations in a large-scale cohort study using capillary electrophoresis-mass spectrometry.

Ishibashi Y, Harada S, Takeuchi A, Iida M, Kurihara A, Kato S, Kuwabara K, Hirata A, Shibuki T, Okamura T, Sugiyama D, Sato A, Amano K, Hirayama A, Sugimoto M, Soga T, Tomita M, Takebayashi T

Scientific reports (Scientific Reports) 11 ( 1 ) 7407 2021.04

Research paper (scientific journal), ISSN 2045-2322

Currently, large-scale cohort studies for metabolome analysis have been launched globally. However, only a few studies have evaluated the reliability of urinary metabolome analysis. This study aimed to establish the reliability of urinary metabolomic profiling in cohort studies. In the Tsuruoka Metabolomics Cohort Study, 123 charged metabolites were identified and routinely quantified using capillary electrophoresis-mass spectrometry (CE-MS). We evaluated approximately 750 quality control (QC) samples and 6,720 participants’ spot urine samples. We calculated inter- and intra-batch coefficients of variation in the QC and participant samples and technical intraclass correlation coefficients (ICC). A correlation of metabolite concentrations between spot and 24-h urine samples obtained from 32 sub-cohort participants was also evaluated. The coefficient of variation (CV) was less than 20% for 87 metabolites (70.7%) and 20–30% for 19 metabolites (15.4%) in the QC samples. There was less than 20% inter-batch CV for 106 metabolites (86.2%). Most urinary metabolites would have reliability for measurement. The 96 metabolites (78.0%) was above 0.75 for the estimated ICC, and those might be useful for epidemiological analysis. Among individuals, the Pearson correlation coefficient of 24-h and spot urine was more than 70% for 59 of the 99 metabolites. These results show that the profiling of charged metabolites using CE-MS in morning spot human urine is suitable for epidemiological metabolomics studies.

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A Novel Risk Stratification System for Ischemic Stroke in Japanese Patients With Non-Valvular Atrial Fibrillation.

Okumura K, Tomita H, Nakai M, Kodani E, Akao M, Suzuki S, Hayashi K, Sawano M, Goya M, Yamashita T, Fukuda K, Ogawa H, Tsuda T, Isobe M, Toyoda K, Miyamoto Y, Miyata H, Okamura T, Sasahara Y, J-RISK AF Research Group.

Circulation journal : official journal of the Japanese Circulation Society (Circulation Journal) 85 ( 8 ) 1254 - + 2021.03

Research paper (scientific journal), ISSN 1346-9843

Background: Recently, identification of independent risk factors for ischemic stroke in Japanese non-valvular atrial fibrillation (NVAF) patients was made by analyzing the 5 major Japanese registries: J-RHYTHM Registry, Fushimi AF Registry, Shinken Database, Keio interhospital Cardiovascular Studies, and the Hokuriku-Plus AF Registry. Methods and Results: The predictive value of the risk scheme in Japanese NVAF patients was assessed. Of 16,918 patients, 12,289 NVAF patients were analyzed (mean follow up, 649±181 days). Hazard ratios (HRs) of each significant, independent risk factor were determined by using adjusted Cox-hazard proportional analysis. Scoring system for ischemic stroke was created by transforming HR logarithmically and was estimated by c-statistic. During the 21,820 person-years follow up, 241 ischemic stroke events occurred. Significant risk factors were: being elderly (aged 75-84 years [E], HR=1.74), extreme elderly (≥85 years [EE], HR=2.41), having hypertension (H, HR=1.60), previous stroke (S, HR=2.75), type of AF (persistent/permanent) (T, HR=1.59), and low body mass index <18.5 kg/m2(L, HR=1.55) after adjusting for oral anticoagulant treatment. The score was assigned as follows: 1 point to H, E, L, and T, and 2 points to EE and S (HELT-E2S2score). The C-statistic, using this score, was 0.681 (95% confidence interval [CI]=0.647-0.714), which was significantly higher than those using CHADS2(0.647; 95% CI=0.614-0.681, P=0.027 for comparison) and CHA2DS2-VASc scores (0.641; 95% CI=0.608-0.673, P=0.008).

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Association of the Estimated Coronary Artery Incidence Risk According to the Japan Atherosclerosis Society Guidelines 2017 with Cardio-Ankle Vascular Index.

Sata M, Okamura T, Harada S, Sugiyama D, Kuwabara K, Hirata A, Takeuchi A, Iida M, Kato S, Matsumoto M, Kurihara A, Takebayashi T

Journal of atherosclerosis and thrombosis (Journal of Atherosclerosis and Thrombosis) 28 ( 12 ) 1266 - 1274 2021.03

Research paper (scientific journal), ISSN 1340-3478

Aims: The categories in the comprehensive lipid and risk management guidelines were proposed by the Japan Atherosclerosis Society (JAS Guidelines 2017), which adopted the estimated 10 year absolute risk of coronary artery disease (CAD) incidence in the Suita score. We examined whether those categories were concordant with the degree of arterial stiffness. Methods: In 2014, the cardio-ankle vascular index (CAVI), an arterial stiffness parameter, was measured in 1,972 Japanese participants aged 35–74 years in Tsuruoka City, Yamagata Prefecture, Japan. We examined the mean CAVI and the proportion and odds ratios (ORs) of CAVI ≥ 9.0 on the basis of the following three management classifications using the analysis of variance and logistic regression: “Category I (Low risk),” “Category II (Middle risk),” and “Category III (High risk).” Results: The mean CAVI and proportion of CAVI ≥ 9.0 were 8.6 and 34.8% among males and 8.1 and 18.3% among females, respectively. The mean CAVI and proportion of CAVI ≥ 9.0 were associated with an estimated 10 year absolute risk for CAD among males and females, excluding High risk for females. These results were similar to the management classification by the guideline: the multivariable-adjusted ORs (95% confidence intervals) of CAVI ≥ 9.0 among Category II and Category III compared with those among Category I were 2.96 (1.61–5.43) and 7.33 (4.03–13.3) for males and 3.99 (2.55–6.24) and 3.34 (2.16–5.16) for females, respectively. Conclusions: The risk stratification, which was proposed in the JAS Guidelines 2017, is concordant with the arterial stiffness parameter.

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Alcohol drinking and brain morphometry in apparently healthy community-dwelling Japanese men

Syaifullah A.H., Shiino A., Fujiyoshi A., Kadota A., Kondo K., Ito T., Segawa H., Moniruzzaman M., Waki T., Miyagawa N., Tooyama I., Ueshima H., Miura K., Horie M., Nakagawa Y., Yamamoto T., Nakano Y., Ogawa E., Maegawa H., Morino K., Miyazawa I., Watanabe Y., Nozaki K., Andoh A., Tsuru T., Ogita H., Miyamatsu N., Nakamura Y., Torii S., Kadowaki T., Kadowaki S., Suzuki S., Kunimura A., Higashiyama A., Okamura T., Azuma K., Sawamura T., Igase M., Tabara Y., Sekikawa A., Barinas-Mitchell E.J.M., Edmundowicz D., Ohkubo T., Hozawa A., Murakami Y., Okuda N., Arima H., Satoh A., Kita Y., Hisamatsu T., Yanagita M., Abbott R.D., Ohno S., Takashima N., Zaid M., Saito Y.

Alcohol (Alcohol) 90 57 - 65 2021.02

Research paper (scientific journal), ISSN 07418329

© 2020 Elsevier Inc. The clinical implications of alcohol consumption have been extensively examined; however, its effects on brain structures in apparently healthy community-dwellers remain unclear. Therefore, we investigated the relationship between alcohol consumption and brain gray matter volume (GMV) in community-dwelling Japanese men using voxel-based morphometry (VBM). We recruited cognitively intact Japanese men, aged 40–79 years, from a population-based cohort in Shiga, Japan. Brain magnetic resonance imaging was performed, on average, 2 years after demographic and medical information was obtained in 2010–2014. A multivariable linear regression analysis of 639 men was conducted to elucidate the relationship between the amount of alcohol consumed and GMV. VBM statistics were analyzed by threshold-free cluster enhancement with a family-wise error rate of <0.05. The results obtained demonstrated that the amount of alcohol consumed was associated with lower GMV. The VBM analysis showed lower GMV within the parahippocampal, entorhinal, cingulate, insular, temporal, and frontal cortices and cerebellum in very heavy drinkers (≥42 ethanol g/day) than in non-drinkers. Furthermore, alcohol consumption was associated with a higher white matter lesion volume. These results suggest subclinical structural changes similar to alcohol-related neurological diseases.

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Relationship between non-fasting triglycerides and cardiovascular disease mortality in a 20-year follow-up study of a Japanese general population: NIPPON DATA90.

Hirata A, Okamura T, Hirata T, Sugiyama D, Ohkubo T, Okuda N, Kita Y, Hayakawa T, Kadota A, Kondo K, Miura K, Okayama A, Ueshima H

Journal of epidemiology (Journal of Epidemiology) 32 ( 7 ) 303 - 313 2021.01

Research paper (scientific journal), ISSN 0917-5040

Background: Non-fasting triglycerides (TG) are considered a better predictor of cardiovascular disease (CVD) than fasting TG. However, the effect of non-fasting TG on fatal CVD events remains unclear. In the present study, we aimed to explore the relationship between non-fasting TG and CVD mortality in a Japanese general population. Methods: A total of 6,831 participants without a history of CVD, in which those who had a blood sampling over 8 hours or more after a meal were excluded, were followed for 18.0 years. We divided participants into seven groups according to non-fasting TG levels: ≤59 mg=dL, 60–89 mg=dL, 90–119 mg=dL, 120–149 mg=dL, 150–179 mg=dL, 180–209 mg=dL, and ≥210 mg=dL, and estimated the multivariable-adjusted hazard ratios (HRs) of each TG group for CVD mortality after adjusting for potential confounders, including high density lipoprotein cholesterol. Additionally, we performed analysis stratified by age <65 and ≥65 years. Results: During the follow-up period, 433 deaths due to CVD were detected. Compared with a non-fasting TG of 150–179 mg=dL, non-fasting TG ≥210 mg=dL was significantly associated with increased risk for CVD mortality (HR 1.56: 95% CI, 1.01–2.41). Additionally, lower levels of non-fasting TG were also significantly associated with increased risk for fatal CVD. In participants aged ≥65 years, lower levels of non-fasting TG had a stronger impact on increased risk for CVD mortality, while higher levels of non-fasting TG had a stronger impact in those aged <65 years. Conclusion: In a general Japanese population, we observed a U-shaped association between non-fasting TG and fatal CVD events.

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Tracking Pattern of Total Cholesterol Levels from Childhood to Adolescence in Japan.

Osawa E, Asakura K, Okamura T, Suzuki K, Fujiwara T, Maejima F, Nishiwaki Y

Journal of atherosclerosis and thrombosis (Journal of atherosclerosis and thrombosis) 29 ( 1 ) 38 - 49 2021.01

Research paper (scientific journal), ISSN 1340-3478

AIMS: This study aimed to evaluate the tracking pattern of serum total cholesterol (TC) levels among Japanese children using data collected continuously for 9 years and examine the relationship between childhood and adulthood TC levels. METHODS: TC levels of 2,608 first grade primary school children enrolled during 1981-2014 from two Japanese towns were measured during annual health check-ups. Nine-year trajectories of estimated TC levels stratified by TC quartiles in the first grade were analyzed using a mixed effects model. Adulthood TC levels were measured in participants who underwent health check-ups in the same area. RESULTS: Overall, 1,322 boys and 1,286 girls in the first grade of a primary school were followed for 9 years. Trajectories of TC levels during the period stratified by TC quartiles in the first grade differed significantly and did not cross each other for both sexes. Childhood data of 242 adult participants were linked with their adulthood data; the mean of age was late 20s for both sexes. The average TC levels in adulthood increased from the first to the fourth quartile in the first grade. Additionally, trajectories of TC levels differed between boys and girls. The later the admission year, the more elevated the TC levels in girls. CONCLUSION: Among Japanese children, TC levels were strongly tracked from childhood to adolescence for 9 years, and elevated TC levels in childhood were related to elevated TC levels in adulthood. Maintaining appropriate TC levels during childhood may be important to prevent future coronary artery diseases.

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Validity of a selective recall method for assessing water intake and its relationship with hydration status

Uchida T., Nakamura Y., Tanaka H., Nakamura S., Okamura T., Watanabe H., Murayam N.

EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES (European Review for Medical and Pharmacological Sciences) 25 ( 21 ) 6623 - 6632 2021

ISSN 1128-3602

OBJECTIVE: We previously established a descriptive dietary record method that accurately quantifies habitual water intake from food and beverages, to ascertain the relationship between water intake and health. Here, we verified the validity of a selective recall method, which is easy for users to answer and analyze. PATIENTS AND METHODS: Japanese men and women aged 20-44 years (n = 16) and 45-64 years (n = 16) participated over three working days and one non-working day. The day following each of the surveyed days, participants collected their first morning urine for urinalysis and completed a selective recall and descriptive dietary record questionnaire. RESULTS: The two methods of determining water intake were positively correlated (r = 0.94, p < 0.0001). Water intake volumes from non-alcoholic beverages (r = 0.94, p < 0.0001), alcoholic beverages (r = 1.00, p < 0.0001), and food (r = 0.72, p < 0.0001), calculated using the two methods, exhibited strong correlation. No correlation was observed between urinalysis parameters and total water intake. A significant, negative correlation was observed between urine osmolarity and total water intake in men (r = -0.55, p = 0.0011) and women (r = -0.51, p = 0.0032) aged 20-44 years. CONCLUSIONS: Selective recall is a valid method for assessing water intake from food and beverages.

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Development of a Cardiovascular Disease Risk Prediction Model Using the Suita Study, a Population-Based Prospective Cohort Study in Japan (vol 27, pg 1160, 2020)

Nakai Michikazu, Watanabe Makoto, Kokubo Yoshihiro, Nishimura Kunihiro, Higashiyama Aya, Takegami Misa, Nakao Yoko M., Okamura Tomonori, Miyamoto Yoshihiro

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS 28 ( 3 ) 304 - 304 2021

Research paper (scientific journal), ISSN 1340-3478

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Prevalence, Characteristics, and Impact of Frailty in Patients with Functional Tricuspid Regurgitation.

Saji M, Yoshikawa T, Takayama M, Izumi Y, Takamisawa I, Okamura T, Shimizu H, Lim DS, Latib A, Isobe M, Fukuda K

International heart journal (International Heart Journal) 62 ( 6 ) 1280 - 1286 2021

Research paper (scientific journal), ISSN 1349-2365

Little is known as regards frailty in patients with functional tricuspid regurgitation (FTR). Thus, in this study, we aimed to investigate the prevalence, characteristics, and impact of frailty on patients with severe FTR. This prospective study included 110 consecutive patients with severe FTR who were assessed via transtho-racic echocardiography at an outpatient clinic. Patients were dichotomized using short physical performance bat-tery (SPPB). To better understand the whole picture of frailty in patients with FTR, other frailty scales were also assessed (frailty checklist, clinical frailty scale, gait speed, and Columbia frailty scale). The primary end-point was the combination of all-cause mortality and heart failure hospitalization. According to each definition of frailty, 28%-46% were identified to be frail. Those with SPPB score of < 9 were older, had greater New York Heart Association (NYHA) functional classification, and had lower albumin level and estimated glomerular filtration rate compared with those with SPPB score of ≥9. They also have smaller tricuspid valve coaptation depth and worse right ventricular fractional area change (RV-FAC) than those with SPPB score of ≥9 despite having similar TR severity. The primary endpoint at 1 year was noted in 31% of patients. The SPPB score has excellent discriminatory performance for predicting the primary endpoint (area under the curve 0.82, 95% confidence interval [CI] 0.76-0.91) in receiver operating characteristic analysis and was independently associated with the primary endpoint after adjustment in multivariate analysis (adjusted haz-ard ratio 0.81, 95% CI, 0.73-0.90; P < 0.001). Frailty has been widely prevalent in the elderly patient population with FTR; in fact, it has been deter-mined to be strong parameter for poor outcomes.

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Validity Assessment of Self-reported Medication Use for Hypertension, Diabetes, and Dyslipidemia in a Pharmacoepidemiologic Study by Comparison With Health Insurance Claims.

Matsumoto M, Harada S, Iida M, Kato S, Sata M, Hirata A, Kuwabara K, Takeuchi A, Sugiyama D, Okamura T, Takebayashi T

Journal of epidemiology (Journal of Epidemiology) 31 ( 9 ) 495 - 502 2020.12

Research paper (scientific journal), ISSN 0917-5040

Background: Although self-reported questionnaires are widely employed in epidemiologic studies, their validity has not been sufficiently assessed. The aim of this study was to evaluate the validity of a self-reported questionnaire on medication use by comparison with health insurance claims and to identify individual determinants of discordance in the Tsuruoka Metabolomics Cohort Study. Methods: Participants were 2,472 community-dwellers aged 37 to 78 years from the Tsuruoka Metabolomics Cohort Study. Information on lifestyle and medications was collected through a questionnaire. Sensitivity and specificity were determined using health insurance claims from November 2014 to March 2016, which were used as a standard. Potential determinants of discordance were assessed using multivariable logistic regression. Results: The self-reported questionnaire on medication use showed high validity. Sensitivity and specificity were 0.95 (95% CI, 0.93–0.96) and 0.97 (95% CI, 0.96–0.98) for antihypertensive medications, 0.94 (95% CI, 0.91–0.97) and 0.98 (95% CI, 0.98–0.99) for diabetes medications, and 0.84 (95% CI, 0.82–0.87) and 0.98 (95% CI, 0.97–0.99) for dyslipidemia medications, respectively. Males without high education and those who currently smoke cigarettes were found to be associated with discordant reporting which affected sensitivity, especially those with medication use for dyslipidemia. Conclusions: In this population-based cohort study, we found that the self-reported questionnaire on medication use was a valid measure to capture regular medication users. Sensitivity for dyslipidemia medications was lower than those for the other medications. Type of medication, sex, education years, and smoking status influenced discordance, which affected sensitivity in self-reporting.

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Risk Factors That Most Accurately Predict Coronary Artery Disease Based on the Duration of Follow-up　- NIPPON DATA80.

Okami Y, Ueshima H, Nakamura Y, Kondo K, Kadota A, Okuda N, Ohkubo T, Miyamatsu N, Okamura T, Miura K, Okayama A, NIPPON DATA80 Research Group.

Circulation journal : official journal of the Japanese Circulation Society (Circulation journal : official journal of the Japanese Circulation Society) 85 ( 6 ) 908 - 913 2020.12

Research paper (scientific journal), ISSN 1346-9843

BACKGROUND: This study assessed sex-specific time-associated changes in the impact of risk factors on coronary artery disease (CAD) mortality in a general population over long-term follow-up.Methods and Results:A prospective longitudinal cohort study was conducted on representative Japanese populations followed up for 29 years. Data from 8,396 participants (3,745 men, 4,651 women) were analyzed. The sex-specific multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of 4 risk factors (smoking, diabetes, serum total cholesterol [TC], and systolic blood pressure [SBP]) for CAD mortality were calculated at baseline and at 10, 15, 20, 25, and 29 years of follow-up. In men, smoking (HR 3.23; 95% CI 1.16-9.02) and a 1-SD increase in TC (HR 1.82; 95% CI 1.29-2.57) were strongly associated with a higher risk of CAD in the first 10 years, but this association decreased over time. Diabetes (HR 2.30; 95% CI 1.37-3.85) and a 1-SD increase in SBP (HR 1.23; 95% CI 1.00-1.50) were strongly correlated with a higher risk of CAD after 29 years). In women, diabetes was correlated with CAD after 20 years (HR 2.53; 95% CI 1.19-5.36) and this correlation persisted until after 29 years (HR 2.47; 95% CI 1.40-4.35). CONCLUSIONS: The duration of follow-up needed for the accurate assessment of risk factors for CAD mortality varies according to risk factor and sex.

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Physique at Birth and Cardiovascular Disease Risk Factors in Japanese Urban Residents: the KOBE Study.

Umemoto K, Kubo S, Nishida Y, Higashiyama A, Kawamura K, Kubota Y, Hirata T, Hirata A, Sata M, Kuwabara K, Miyazaki J, Kadota A, Iida M, Sugiyama D, Miyamatsu N, Miyamoto Y, Okamura T

Journal of atherosclerosis and thrombosis (Journal of Atherosclerosis and Thrombosis) 29 ( 2 ) 188 - 199 2020.12

Research paper (scientific journal), ISSN 1340-3478

Aim: This study investigated the relationship between birth physique and cardiovascular risk factors in Japanese urban residents aged 40 years and more. Methods: A self-administered questionnaire on birth physique was performed among 624 individuals (165 men and 459 women) who participated in the KOBE study. We examined whether self-reported birth physique and available recorded birth weights matched for 72 participants. Then the association between birth physique and risk factors for all participants was examined by gender. Body size at birth in the questionnaire (large, medium, small) was set as an exposure and laboratory values from the baseline survey (2010-2011) were used as outcomes. Results: Mean (standard deviation) recorded birth weight of 72 participants was 3665 (318), 3051 (300), and 2653 (199) g, in the large, medium, and small group, respectively. In the analysis for all participants, odds ratio for having both hypertension and impaired glucose tolerance were significantly higher in the small versus large birth weight group, which was 7.42 (95% CI 1.75–31.50) for men and 4.44 (95% CI 1.14–17.30) for women after adjusting for age, body mass index, smoking/alcohol/exercise habits, and menstrual status in women. Similar results were observed in participants with recorded birth weight. Conclusions: The present study indicates that individuals with small physique at birth might be at higher risk for hypertension and impaired glucose tolerance in middle age compared to those with large birth weight.

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Association of Red Meat Intake with the Risk of Cardiovascular Mortality in General Japanese Stratified by Kidney Function: NIPPON DATA80.

Segawa H, Kondo K, Kadota A, Yamauchi H, Ohno S, Tanaka-Mizuno S, Okuda N, Miyagawa N, Arima H, Okamura T, Miura K, Okayama A, Ueshima H, The Nippon Data Research Group

Nutrients (Nutrients) 12 ( 12 ) 1 - 10 2020.11

Research paper (scientific journal)

The consumption of red meat has been recommended for individuals with reduced kidney function. However, red meat intake was recently suspected to increase cardiovascular disease (CVD) risk. We evaluated the association of red meat intake with CVD mortality risk in Japanese with/without reduced kidney function. Overall, 9112 participants of a Japanese national survey in 1980, aged ≥30 years, were followed for 29 years. Red meat intake was assessed using weighed dietary record. Cox proportional hazards models were used to estimate the hazard ratio (HR) of CVD mortality according to sex-specific tertiles of red meat intake. We also performed stratified analyses with/without reduced kidney function defined as estimated glomerular filtration rate less than 60 mL/min/1.73 m . Red meat intake was not associated with CVD mortality risk in men and women. In stratified analyses, the HR of the highest compared with the lowest tertile of red meat intake was lower only in women with reduced kidney function (0.67, 95% confidence interval 0.46–0.98). In conclusion, there were no clear associations between red meat intake and CVD mortality risk in Japanese population; however, a higher intake of red meat was associated with lower risk of future CVD mortality in women with reduced kidney function. 2

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Exercise Habits Are Associated with Improved Long-Term Mortality Risks in the Nationwide General Japanese Population: A 20-Year Follow-Up of the NIPPON DATA90 Study.

Takatsuji Y, Ishiguro A, Asayama K, Ohkubo T, Miura K, Kadota A, Yanagita M, Fujiyoshi A, Arima H, Miyagawa N, Takashima N, Kita Y, Hayakawa T, Kikuya M, Nakamura Y, Okayama A, Okamura T, Ueshima H, NIPPON DATA90 Research Group.

The Tohoku journal of experimental medicine (The Tohoku journal of experimental medicine) 252 ( 3 ) 253 - 262 2020.11

Research paper (scientific journal), ISSN 0040-8727

Exercise habits are known as a protective factor for a variety of diseases and thus recommended worldwide; however, few studies have examined long-term effects of exercise habits on mortality. We continuously monitored death status in a nationwide population sample of 7,709 eligible persons from the National Integrated Project for Prospective Observation of Noncommunicable Disease and its Trends in the Aged in 1990 (NIPPON DATA90), for which baseline data were obtained in 1990. To investigate the long-term impact of baseline exercise habits, we calculated the relative risk of non-exercisers (participants without regular voluntary exercise habits) in reference to exercisers (those with these habits) for all-cause or cause-specific mortality using a Cox proportional hazard model, in which the following confounding factors were appropriately adjusted: sex, age, body mass index, total energy intake, smoking, drinking, and history of cardiovascular disease. During a median 20 years of follow-up, 1,747 participants died, 99 of heart failure. The risk for all-cause mortality was 12% higher in non-exercisers than in exercisers (95% confidence interval, 1%-24%), which was also observed for mortality from heart failure, as 68% higher in non-exercisers than in exercises (95% confidence interval, 3%-173%). These associations were similarly observed when the participants were divided to subgroups by sex, age, and the light, moderate, or vigorous intensity of physical activity, without any significant heterogeneities (P > 0.1). The present study has revealed significant impact of exercise habits on long-term mortality risks, supporting worldwide recommendations for improvement of exercise habits.

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Estimation of 10-Year Risk of Death from Coronary Heart Disease, Stroke, and Cardiovascular Disease in a Pooled Analysis of Japanese Cohorts: EPOCH-JAPAN.

Li Y, Yatsuya H, Tanaka S, Iso H, Okayama A, Tsuji I, Sakata K, Miyamoto Y, Ueshima H, Miura K, Murakami Y, Okamura T, EPOCH-JAPAN Research Group.

Journal of atherosclerosis and thrombosis (Journal of Atherosclerosis and Thrombosis) 28 ( 8 ) 816 - 825 2020.10

Research paper (scientific journal), ISSN 1340-3478

Aims: We aimed to develop and validate risk prediction models to estimate the absolute 10-year risk of death from coronary heart disease (CHD), stroke, and cardiovascular disease (CVD). Methods: We evaluated a total of 44,869 individuals aged 40-79 years from eight Japanese prospective cohorts to derive coefficients of risk equations using cohort-stratified Cox proportional hazard regression models. Discrimination (C-index) of the equation was examined in each cohort and summarised using random-effect metaanalyses. Calibration of the equation was assessed using Hosmer-Lemeshow chi-squared statistic. Results: Within a median follow-up of 12.7 years, we observed 765 deaths due to CVD (276 CHDs and 489 strokes). After backward selection, age, sex, current smoking, systolic blood pressure (SBP), proteinuria, prevalent diabetes mellitus, the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDLC), interaction terms of age by SBP, and age by current smoking were retained as predictors for CHD. Sex was excluded in the stroke equation. We did not consider TC/HDLC as a risk factor for the stroke and CVD equations. The pooled C-indices for CHD, stroke, and CVD were 0.83, 0.80, and 0.81, respectively, and the corresponding p-values of the Hosmer-Lemeshow tests were 0.18, 0.003, and 0.25, respectively. Conclusions: Risk equations in the present study can adequately estimate the absolute 10-year risk of death from CHD, stroke, and CVD. Future work will evaluate the system as an education and risk communication tool for primary prevention of CHD and stroke.

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The relationship between serum levels of LOX-1 ligand containing ApoAI as a novel marker of dysfunctional HDL and coronary artery calcification in middle-aged Japanese men.

Hirata A, Kakino A, Okamura T, Usami Y, Fujita Y, Kadota A, Fujiyoshi A, Hisamatsu T, Kondo K, Segawa H, Sawamura T, Miura K, Ueshima H, SESSA Research Group.

Atherosclerosis (Atherosclerosis) 313 20 - 25 2020.09

Research paper (scientific journal), ISSN 0021-9150

© 2020 Elsevier B.V. Background and aims: Dysfunctional high-density lipoprotein (HDL) is a risk factor for cardiovascular disease (CVD) beyond HDL concentrations. Recently, a novel method has been introduced to measure LOX-1 ligand containing apolipoprotein AI (LAA), which is an indicator of various types of modified HDL with binding capacity to LOX-1 and related to impaired anti-atherogenic functions of HDL. This study aimed to examine the relationship between LAA as a novel marker of dysfunctional HDL and coronary artery calcification (CAC). Methods: We selected 910 community-dwelling Japanese men aged 40–79 years without a history of CVD. The odds ratios per 1SD of LAA for the presence of CAC (Agatston score >10) were estimated using logistic regression model adjusted for confounders, including HDL-C or HDL particle (HDL-P) concentration. In addition, we performed further analysis stratified by age (<65 and ≥ 65 years). Results: The mean age of the participants was 63.6 years, and the median LAA was 187.0 ng/mL. The prevalent CAC was 46.2%. The multivariable adjusted odds ratio (95% confidence interval) per 1SD of LAA for CAC was 1.14 (0.96–1.36) for all participants. After stratification by age, multivariable adjusted odds ratios per 1SD of LAA were 1.34 (1.02–1.76) and 0.97 (0.77–1.23) in men aged <65 and ≥ 65 years, respectively. Conclusions: The present study showed that LAA was associated with CAC independent of HDL-C or HDL-P in middle-aged Japanese men. This finding suggests that LAA might be an early marker for CVD events. Future longitudinal studies are warranted.

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Differences between home blood pressure and strictly measured office blood pressure and their determinants in Japanese men.

Kadowaki S, Kadowaki T, Hozawa A, Fujiyoshi A, Hisamatsu T, Satoh A, Arima H, Tanaka S, Torii S, Kondo K, Kadota A, Masaki K, Okamura T, Ohkubo T, Miura K, Ueshima H, SESSA Research Group.

Hypertension research : official journal of the Japanese Society of Hypertension (Hypertension Research) 44 ( 1 ) 80 - 87 2020.08

Research paper (scientific journal), ISSN 0916-9636

© 2020, The Japanese Society of Hypertension. Conventional office blood pressure (OBP) and home blood pressure (HBP) measurements are often inconsistent. The purpose of this research was (1) to test whether strictly measured OBP values with sufficient rest time before measurement (st-OBP) is comparable to HBP at the population level and (2) to ascertain whether there are particular determinants for the difference between HBP and st-OBP at the individual level. Data from a population-based group of 1056 men aged 40–79 years were analyzed. After a five-min rest, st-OBP was measured twice. HBP was measured after a 2-min rest every morning for seven consecutive days. To determine factors related to ΔSBP (HBP minus st-OBP measurements), multiple linear regression analyses and analyses of covariance were performed. While st-OBP and HBP were comparable (136.5 vs. 137.2 mmHg) at the population level, ΔSBP varied with a standard deviation of 13.5 mmHg. Smoking was associated with a larger ΔSBP regardless of antihypertensive usage, and BMI was associated with a larger ΔSBP in participants using antihypertensive drugs. The adjusted mean ΔSBP in the highest BMI tertile category was 4.6 mmHg in participants taking antihypertensive drugs. st-OBP and HBP measurements were comparable at the population level, although the distribution of ΔSBP was considerably broad. Smokers and obese men taking antihypertensive drugs had higher HBP than st-OBP, indicating that their blood pressure levels are at risk of being underestimated. Therefore, this group would benefit from the addition of HBP measurements.

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Guidelines on the Clinical Evaluation of Medicinal Products for Treatment of Dyslipidemia.

Yamashita S, Masuda D, Akishita M, Arai H, Asada Y, Dobashi K, Egashira K, Harada-Shiba M, Hirata K, Ishibashi S, Kajinami K, Kinoshita M, Kozaki K, Kuzuya M, Ogura M, Okamura T, Sato K, Shimano H, Tsukamoto K, Yokode M, Yokote K, Yoshida M

Journal of atherosclerosis and thrombosis 27 ( 11 ) 1246 - 1254 2020.08

Research paper (scientific journal), ISSN 1340-3478

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Estimated 24 h urinary sodium-to-potassium ratio is related to renal function decline: A 6-year cohort study of japanese urban residents

Hattori H., Hirata A., Kubo S., Nishida Y., Nozawa M., Kawamura K., Hirata T., Kubota Y., Sata M., Kuwabara K., Higashiyama A., Kadota A., Sugiyama D., Miyamatsu N., Miyamoto Y., Okamura T.

International Journal of Environmental Research and Public Health (International Journal of Environmental Research and Public Health) 17 ( 16 ) 1 - 12 2020.08

Research paper (scientific journal), ISSN 16617827

© MDPI AG. All rights reserved. The effect of the sodium-to-potassium ratio (Na/K) on renal function within the clinically normal range of renal function are limited. We investigated the effects of an estimated 24 h urinary Na/K (e24hUNa/K) on a 6-year renal function decline among 927 urban Japanese community dwellers with no history of cardiovascular diseases and medication for hypertension, diabetes, or dyslipidemia. We partitioned the subjects into quartiles according to the e24hUNa/K. The estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration (CKD/EPI) formula and renal function decline was defined as an absolute value at or above the third quartile of the eGFR decline rate. A multivariable logistic regression model was used for estimation. Compared with the first quartile of the e24hUNa/K, multivariable-adjusted odds ratios (ORs) for eGFR decline in the second, third, and fourth quartiles were 0.96 (95% confidence interval: 0.61–1.51), 1.06 (0.67–1.66), and 1.65 (1.06–2.57), respectively. These results were similar when the simple spot urine Na/K ratio was used in place of the e24hUNa/K. Apparently healthy urban residents with an almost within normal range mean baseline eGFR and high e24hUNa/K ratios had an increased risk for a future decline in renal function. Reducing the Na/K ratio may be important in the prevention of chronic kidney disease in its early stage.

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